Pentapeptide enkephalin analogues that possess delta opioid antagonist activity will be modified with a variety of electrophilic substitutents at the Phe4 residue in order to develop ligands that selectively or specifically block delta receptors in a nonequilibrium fashion. These ligands will be tested in vitro on the mouse vas deferens and guinea pig ileum preparations in order to evaluate the selectivity and nonequilibrium nature of the effect. Receptor binding studies will be conducted to obtain additional support for covalent bonding to delta sites. In order to evaluate and refine a model for morphine tolerance, the binding of the mu-specific nonequilibrium antagonist, [3H]Beta-FNA, to brain slices from naive and tolerant mice will be investigated.